复制压力促进细胞通过挤出消除
Vivek K Dwivedi1, Carlos Pardo-Pastor2, Rita Droste1
1Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.
Nature
|May 6, 2021
概括
细胞挤出通过复制压力消除细胞,这是动物中保存的过程. 这种涉及ATR-CHK1和p53的机制在哺乳动物中起到瘤抑制作用.
科学领域:
- 细胞生物学
- 发育生物学
- 遗传学
背景情况:
- 细胞挤出是一种重要的细胞清除过程,在多种生物体中保存着.
- 细胞挤出失调与上皮疾病,包括癌症有关.
- 驱动细胞挤出的精确分子机制尚未完全理解.
研究的目的:
- 研究细胞挤出背后的机制.
- 通过全基因组选,识别控制细胞挤出的基因.
- 确定复制应激在细胞挤出中的作用.
主要方法:
- 在Caenorhabditis elegans胚胎中进行全基因组RNA干扰选.
- 进行实时成像实验以分析细胞挤出动态.
- 用于诱导哺乳动物上皮细胞的复制应激.
主要成果:
- 鉴定出具有S相特定功能的细胞循环基因,对挤出至关重要.
- 证明挤出细胞经历并通过ATR和CHK1响应复制压力.
- 显示阻断S相进入或复制应激反应会抑制挤出.
- 通过基尿素诱导的复制应激在哺乳动物细胞中的诱导挤出,依赖于ATR-CHK1和p53.
结论:
- 复制应激诱导的细胞挤出在动物物种中保持.
- 这一过程是细胞消除的原始机制.
- 通过复制压力介导的细胞挤出可以作为哺乳动物的瘤抑制剂.
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